Approach Considerations
Neonatal purpura fulminans
In a neonate with neonatal purpura fulminans, immediate treatment with platelet concentrate is recommended to reverse the thrombocytopenia and the bleeding manifestations. The neonate often develops disseminated intravascular coagulation (DIC). In the absence of signs of generalized bloodstream infection, deficiencies of the anticoagulant factors protein C, protein S, and antithrombin III (ATIII) remain important considerations. Consequently, the endogenous activity of these anticoagulant factors must be assessed by means of a chromogenic assay.
With a provisional diagnosis of purpura fulminans due to protein C deficiency, fresh frozen plasma (FFP) transfusion must be started. The FFP can later be replaced with low-molecular-weight heparin (LMWH). Subsequently, oral anticoagulation with warfarin must be instituted. Debridement of the dead tissue is mandatory. The protein C, protein S, and ATIII genes must be analyzed both in the patient and in the parents.
These patients require long-term oral anticoagulation, which, if well tolerated, may be sufficient to permit them to remain free of coagulopathy throughout life. [21] If the genetic assays reveal a defect in the protein C or ATIII genes, the protein C or ATIII concentrates may be used to correct this coagulation disorder.
In 2018 guidelines released by the American Society of Hematology (ASH) on the management of venous thromboembolism, the guidelines panel remarked that protein C replacement offers better long-term effectiveness than does anticoagulation in pediatric patients with purpura fulminans arising from homozygous protein C deficiency (although the panel also cited a concern that protein C therapy may be prohibitively expensive). In addition, the ASH guidelines suggested that during an acute episode in such pediatric patients, treatment involve anticoagulation not by itself but in combination with protein C replacement. [22]
Idiopathic purpura fulminans
In 1995, Sheridan et al described a management strategy for idiopathic purpura fulminans with multiple organ failure in children. In three cases in the report, the purpura fulminans involved a large percentage of the patients’ body surface areas. One patient, a 15-year-old boy, had skin lesions on 55% of his body surface area. Another patient, an 11-month-old girl, was affected on 25% of her body surface area. The third patient, a 2-year-old boy, had evidence of purpura fulminans on 55% of his body surface area. The pathogenesis of purpura fulminans was not known but probably involved acute transient decreases in protein C, protein S, or ATIII. [23]
The successful management of meningococcal sepsis in these patients was facilitated by early diagnosis and aggressive antibiotic therapy. [23] Management of purpura fulminans was particularly challenging in these cases because the children had evidence of multiple organ failure.
To better understand the current management of idiopathic purpura fulminans, seven burn centers performed a 10-year retrospective chart review of patients who were diagnosed with idiopathic purpura fulminans. [24] A total of 70 patients were identified, with a mean patient age of 13 years. Neisseria meningitidis [25] was the most common pathogen identified in infants and adolescents, while Streptococcus species predominated in adults.
In the patients studied, acute management consisted of antibiotic treatment, volume resuscitation, and ventilatory and inotropic support. [24] Protein C replacement was performed in only 9% of the cases. One fourth of the patients required amputation of all of the extremities. When performed early, fasciotomies may reduce the depth of soft tissue involvement and the extent of amputation. Although the overall mortality in this study was only 13%, the surgeons believed this number to be inaccurately low because it did not reflect the number of patients who succumbed to sepsis in facilities outside the multicenter study group.
In general, the authors recommend a conservative approach to treatment of idiopathic purpura fulminans that includes excising gangrenous areas after they have been demarcated from purpuric and indeterminate zones. In the presence of infection, however, early aggressive surgical debridement is essential to prevent invasive wound sepsis. When compartment syndrome is suspected in patients with tense limbs and distal ischemia, early fasciotomy is recommended. If established gangrene is present, conservative amputation is warranted.
Manco-Johnson and Knapp-Clevenger described the use of activated protein C (APC) in a 14-year-old girl with protein C deficiency due to idiopathic purpura fulminans. [26] At the end of the APC infusions, all skin lesions of purpura fulminans were resolved. The patient experienced no adverse reactions to APC. The authors concluded that APC is safe and effective for the treatment of purpura fulminans with severe genetic protein C deficiency.
Recognition of the pathophysiologic mechanism of idiopathic purpura fulminans provides a rational basis for treatment with immediate heparinization and infusion of FFP. [18] In some cases complicated by major vessel thrombosis, the use of tissue plasminogen activator (tPA) may reduce thromboembolic complications.
Acute infectious purpura fulminans
Meningococcemia and infection due to S aureus lead to acute infectious purpura fulminans. Patients with these infections have remarkably reduced levels of APC as a result of dysfunction of the endothelial protein C activation pathway. APC not only acts as an anticoagulant but also serves as an important modulator of the inflammatory response.
Patients who present with acute infectious purpura fulminans should receive broad-spectrum intravenous antibiotic therapy with activity against a variety of pathogens, including N meningitidis, streptococci, and methicillin-resistant S aureus (MRSA).
Consideration should also be given to early administration of APC concentrates to minimize purpura skin injury and to reduce the inflammatory cascade before irreparable tissue injury occurs. [27] Finally, because toxic shock syndrome is mediated by strong antigens, intravenous immunoglobulin (IVIg) therapy should be implemented because these preparations contain significant antibodies against the causative exotoxins. [28]
Because patients with DIC are at risk for acute thrombosis and bleeding, it is difficult to predict which will occur in a specific patient. Given these inherent risks and the lack of evidence available, prophylactic anticoagulation is not currently indicated in the treatment of acute infectious purpura fulminans. [29]
Hyperbaric oxygen therapy (HBOT) has rarely been used in the treatment of purpura fulminans and is not currently considered an important part of its therapy.
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Lesion associated with purpura fulminans in an adult patient. Courtesy of DermNet New Zealand.
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Schistocytes (arrows) on a peripheral smear. Courtesy of Bodhit AN, Stead LG. Altered mental status and a not-so-benign rash. Case Rep Emerg Med. 2011;2011:684572.
Tables
Typical Lab Values in Acute Disseminated Intravascular Coagulation (DIC)* |
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Lab Test |
Acute DIC |
Reference Range |
Platelet count |
< 150,000/L |
150,000-450,000/L |
Fibrinogen |
>340 mg/dL |
170-340 mg/dL |
Prothrombin time (PT) |
>13 seconds |
9-13 seconds |
Activated partial thromboplastin time (aPTT) |
>35 seconds |
23-35 seconds |
D-dimer |
>250 ng/mL |
0-250 ng/mL |
